The E3 ligase Ubr1 deciphers N-terminal location codes for protein translocation quality control

Title The E3 ligase Ubr1 deciphers N-terminal location codes for protein translocation quality control
Lecturer Prof.Davis T.W. Ng 
(Temasek Life Sciences Laboratory, Singapore)
Language English
Date&Time 09/16/2016 (Fri) 13:30~14:30
Venue L12 Seminar Room
Detail The complex organization of eukaryotic cells requires precise logistic systems to correctly deliver and place proteins throughout the cell. Although the transport mechanisms for most proteins are well understood, the mechanisms that monitor and offset the effects of mislocalization are less defined. In protein folding quality control, the existence of two E3 ubiquitin ligases San1 and Ubr1 with partially overlapping substrate specificities was a conundrum. To address this mystery, we systematically modified the amino-termini of a Ubr1 dependent misfolded protein substrate. The pattern that emerged only partially overlapped with the existing N-end rule established by the Varshavsky group for folded proteins. Remarkably, the pattern best fits the sequence pattern for proteins destined for the secretory pathway and mitochondria. Normally, these proteins are transported to locations inaccessible to Ubr1, with the sequences often removed (signal sequences and signal peptides) after translocation. We realized that the sequences would appear in the cytosol only if the proteins fail to translocate, an aberrant and potentially harmful situation. We hypothesized that the N-terminal location code, whose biological relevance was previously unknown, functions inform the cell of translocation failures. Ubr1, whose new N-end rule specificity matches the location code perfectly, functions to recognize and ubiquitinate translcation failures for degradation. We validated this hypothesis directly by examining protein translocation failures of secretory and mitochondrial proteins.
Contact 動物細胞工学
河野憲二 (

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